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Sophiris Moves to Unlock Blockbuster Potential in New Prostate Drug

In the vintage tic-tac-toe TV game show, The Hollywood Squares, one of the classic funny moments occurred when host Peter Marshall asks the question: “True or false—a pea can last as long as 5,000 years.”

Assuming an expression of middle-aged consternation, the late comedian George Gobel answers: “Boy, it sure seems that way sometimes.”

The joke seems funnier—or perhaps more ironical—to me now than it did 30 or 40 years ago. Experts say that benign prostatic hyperplasia (BPH), or an enlarged prostate gland, affects most men in their 60s. As the prostate enlarges, the tissue surrounding the gland prevents it from expanding, causing the prostate to gradually press against the urethra like a pumpkin growing on a garden hose. The condition, which can result in frequent urination or difficult urination, is so common that it is said all men would get an enlarged prostate if they lived long enough.

Lars Ekman, an executive partner in Sofinnova Ventures’ San Diego office, says the condition is serious enough for 15 million men in the U.S. to seek treatment each year, with a comparable number of men in the European Union feeling a similar pressing need. Together, Ekman says they spend about $4 billion a year on a variety of treatments. That’s high, according to the National Institute of Diabetes and Digestion and Kidney Diseases, which put the direct costs of BPH-related medical services in U.S. hospitals and outpatient settings at $1.1 billion. Nevertheless, Ekman says it still amounts to a multi-billion dollar global market with a huge unmet need. “In the prostate there are a number of nerve endings that are related to sexual function,” he says, “and other therapies negatively affect these nerve endings.”

Ekman says he agreed to serve as the executive chairman and president of Sophiris Bio last year, as part of the specialized pharma startup’s move to San Diego from Vancouver, BC, where the company was known as Protox Therapeutics. In Canada, the company completed pre-clinical studies and related testing, which Ekman describes as “a phenomenal job of translating an idea into a real product.”

But Ekman says the Canadian team had never taken an experimental drug through clinical trials, and it was difficult to recruit experienced drug developers to Vancouver. The board decided to make a fresh start, with a new management team and a new round of funding.

So far, the company has raised a total of roughly $55 million from investors, according to a spokesman for Sophiris. Before 2010, the company (which trades on the Toronto Stock Exchange) was funded through a series of small private placement transactions arranged with Canadian investors. In this way, B.C. Advantage Funds, a venture capital business in British Columbia, acquired a “significant” stake in the company.

Sophiris’s re-start officially began in September, 2010, when Protox entered into an investment agreement with Warburg Pincus, the global private equity firm, in which Warburg agreed to invest as much as $34.4 million (CND $35 million) in the company. Of the total, Warburg has invested $27.5 million (CND $28 million) so far.

“The reason I took on this job was that I had spearheaded the due diligence team for Warburg, and I found that this has an absolutely unique asset with a very attractive mechanism for action,” says Ekman. Sofinnova did not participate in the round, but might if the opportunity arises. “Warburg had a chance to do this deal, and they needed to do it fast, so they took the whole deal,” he explains.

Under Ekman, the company also relocated in San Diego, where he says there is an abundance of experienced drug developers. “The current team [about 11 employees and twice as many consultants] has 20 drug approvals under their belt,” he says. In April, the company changed its name to Sophiris Bio, and began trading in Toronto under the new ticker symbol SHS.

Sophiris describes its experimental compound, PRX 302, as a recombinant form of the proaerolysin protein, a large molecule with a specialized group of molecules at one end known as a carboxyl terminus. The carboxyl group acts like a lock that inhibits the protein’s function. If that piece is cleaved off, Ekman says the protein is activated—becoming highly toxic to cells that are close to it.

The particular genius of PRX302 is that the company genetically modified proaerolysin so that only one enzyme—the Prostate Specific Antigen (PSA)—can cleave the carboxyl group from the protein. Ekman says the approach makes the drug highly specific for two reasons—“the PSA is found only on the surface of prostate cells and nowhere else in the body” and because PRX302 is deposited by an ultrasound-guided injection in the area where the prostate meets the ureter. He says the process of injecting the drug is similar to taking a biopsy of the prostate, an outpatient procedure done about 350,000 times a year in the United States.

Once on the surface of the prostate, the drug activates PRX302, causing the protein to drill into the prostate’s cell walls, triggering a programmed cell death known as apoptosis. The toxic effects of the PRX302 protein, he says, cannot be activated elsewhere in the body, Ekman says. The drug’s enzymatic activity appears to have no impact on nerves in the prostate, unlike most conventional treatments, and removes about 15-20 percent of the prostate in the area in closest proximity to the ureter, Ekman says.

“The ureter is completely untouched by the toxin because it’s not coated with PSA, Ekman says. “That part of the prostate is the part that compresses the ureter and makes it difficult to [urinate], so the pressure is alleviated.”

A Sophiris spokesman says the company met the primary endpoint in a randomized mid-stage trial. Of 126 patients treated so far, the company says it has seen no drug-related sexual side effects. The effects of PRX302 lasts at least six months, and Sophiris plans to present its 12-month data in another month or so, Ekman says.

Ekman, who was the president of R&D at Elan before joining Sofinnova in 2008, has more than 28 years in drug development as a senior executive and research scientist. He says the next step involves meeting with FDA regulators this summer to determine the design of final-stage clinical trials. “It will be probably two Phase 3 trials, in the ballpark of 500 to 600 patients in each trial,” Ekman says.

The company also will need to raise additional capital to conduct the pivotal trials. “We are prepared to make the stock available on stock markets other than the Toronto Stock Exchange,” Ekman says, adding that he can’t discuss those plans in detail.

He’s keen to move forward, though. “The commercial opportunity is important,” Ekman says, and I’m at a stage where I want to spend my time in developing meaningful drugs in areas of substantial unmet medical need.” He explains that the current standard of care for treating enlarged prostates involves prescribing alpha-blockers to relax the membrane surrounding the prostrate or some kind of surgery. “So the unmet need is large, and clearly—if the data holds up in the Phase 3 trials—this drug has a blockbuster potential over time.”

Bruce V. Bigelow is the editor of Xconomy San Diego. You can e-mail him at bbigelow@xconomy.com or call (619) 669-8788 Follow @bvbigelow